The main objectives of our proposed research on human hemoglobins and erythrocytes are: (1) to understand the molecular mechanisms for the cooperative oxygenation of human adult hemoglobin by proton nuclear magnetic resonance (NMR) spectroscopy; (2) to correlate the structure-function relationships in human abnormal hemoglobins found in hemoglobinopathies (including sickle cell anemia) by 1H NMR spectroscopy; and (3) to investigate the intracellular environment and metabolism of normal and abnormal human blood by 31P NMR spectroscopy. By choosing appropriate human mutant hemoglobins and by making use of Perutz's atomic models of hemoglobin, we have found that 1H NMR spectroscopy can provide detailed and in some cases unique information about the heme environment, functional properties of the alpha and beta chains, and the nature of subunit interactions during the oxygenation process. By means of 31P NMR spectroscopy, we can determine the intracellular pH and phosphate metabolism of normal and abnormal blood samples. NMR spectroscopy is a non-invasive technique which can indicate what is going on inside the cell without disrupting it. We would like to continue and to expand our NMR studies of hemoglobins and erythrocytes.